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Information on EC 2.7.11.25 - mitogen-activated protein kinase kinase kinase and Organism(s) Schizosaccharomyces pombe and UniProt Accession O14299

for references in articles please use BRENDA:EC2.7.11.25
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EC Tree
IUBMB Comments
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway . Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
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Schizosaccharomyces pombe
UNIPROT: O14299
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The taxonomic range for the selected organisms is: Schizosaccharomyces pombe
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
hide
ATP
+
a [protein]-(L-serine/L-threonine)
=
ADP
+
a [protein]-(L-serine/L-threonine) phosphate
+
a [protein]-(L-serine/L-threonine)
=
+
a [protein]-(L-serine/L-threonine) phosphate
Synonyms
b-raf, c-raf, mekk1, c-mos, apoptosis signal-regulating kinase 1, mixed lineage kinase, ste11, mekk3, map3k1, mapkkk, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
MAP kinase kinase kinase
-
MAP kinase kinase kinase wis4
-
c-mos
-
-
-
-
DLK
-
-
-
-
Dual leucine zipper bearing kinase
-
-
-
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HsNIK
-
-
-
-
Leucine-zipper protein kinase
-
-
-
-
MAP kinase kinase kinase
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MAP kinase kinase kinase mkh1
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MAP kinase kinase kinase win1
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MAPK-upstream kinase
-
-
-
-
MUK
-
-
-
-
NF-kappa beta-inducing kinase
-
-
-
-
Serine/threonine protein kinase NIK
-
-
-
-
ZPK
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:protein phosphotransferase (MAPKKKK-activated)
This enzyme phosphorylates and activates its downstream protein kinase, EC 2.7.12.2, mitogen-activated protein kinase kinase (MAPKK) but requires MAPKKKK for activation. Some members of this family can be activated by p21-activated kinases (PAK/STE20) or Ras. While c-Raf and c-Mos activate the classical MAPK/ERK pathway, MEKK1 and MEKK2 preferentially activate the c-Jun N-terminal protein kinase(JNK)/stress-activated protein kinase (SAPK) pathway [2]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.
CAS REGISTRY NUMBER
COMMENTARY hide
146702-84-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + Atf1
ADP + phosphorylated Atf1
show the reaction diagram
MAPK kinase Atf1 activation
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
required for activation of the MAPK homologue Spc1, and integrity of the Wis1-Spc1 pathway is required for survival in extreme conditions of heat, osmolarity, oxidation or limited nutrition. Phosphorylates Wis1 in vitro and activates it in vivo
-
-
?
ATP + Sty1
ADP + phosphorylated Sty1
show the reaction diagram
MAPK kinase Sty1 activation
-
-
?
ATP + Wis1
ADP + phosphorylated Wis1
show the reaction diagram
-
-
-
?
ATP + Atf1
ADP + phosphorylated Atf1
show the reaction diagram
MAPK kinase Atf1 activation
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + Sty1
ADP + phosphorylated Sty1
show the reaction diagram
MAPK kinase Sty1 activation
-
-
?
ATP + Wis1
ADP + phosphorylated Wis1
show the reaction diagram
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + Atf1
ADP + phosphorylated Atf1
show the reaction diagram
MAPK kinase Atf1 activation
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
required for activation of the MAPK homologue Spc1, and integrity of the Wis1-Spc1 pathway is required for survival in extreme conditions of heat, osmolarity, oxidation or limited nutrition. Phosphorylates Wis1 in vitro and activates it in vivo
-
-
?
ATP + Sty1
ADP + phosphorylated Sty1
show the reaction diagram
MAPK kinase Sty1 activation
-
-
?
ATP + Atf1
ADP + phosphorylated Atf1
show the reaction diagram
MAPK kinase Atf1 activation
-
-
?
ATP + protein
ADP + phosphoprotein
show the reaction diagram
ATP + Sty1
ADP + phosphorylated Sty1
show the reaction diagram
MAPK kinase Sty1 activation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
in cadmium and low glucose medium, Atf1 activation is observed even in the absence of all four fission yeast MAPK kinase kinases (MAPKKKs), whereas in osmotic stress, Atf1 activation is abolished
metabolism
the four MAPKKKs in fission yeast are involved in MAPK activation, e.g. Atf1 or Sty1, in osmotic stress. Osmotic stress, e.g. by KCl, likely mediates the MAPK activation via MAPKKKs, whereas a cadmium or low-glucose condition activates the MAPK in a MAPKKK-independent manner. Protein-tyrosine phosphatases Pyp1 and Pyp2 are negative regulators of the Sty1 MAPK cascade
malfunction
in cadmium and low glucose medium, Atf1 activation is observed even in the absence of all four fission yeast MAPK kinase kinases (MAPKKKs), whereas in osmotic stress, Atf1 activation is abolished
metabolism
the four MAPKKKs in fission yeast are involved in MAPK activation, e.g. Atf1 or Sty1, in osmotic stress. Osmotic stress, e.g. by KCl, likely mediates the MAPK activation via MAPKKKs, whereas a cadmium or low-glucose condition activates the MAPK in a MAPKKK-independent manner. Protein-tyrosine phosphatases Pyp1 and Pyp2 are negative regulators of the Sty1 MAPK cascade
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wood, V.; Gwilliam, R.; Rajandream, M.A.; Lyne, M.; Lyne, R.; et al.
The genome sequence of Schizosaccharomyces pombe
Nature
415
871-880
2002
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe (O74304), Schizosaccharomyces pombe (P28829), Schizosaccharomyces pombe (Q10407)
Manually annotated by BRENDA team
Samejima, I.; Mackie, S.; Fantes, P.A.
Multiple modes of activation of the stress-responsive MAP kinase pathway in fission yeast
EMBO J.
16
6162-6170
1997
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Shieh, J.C.; Wilkinson, M.G.; Buck, V.; Morgan, B.A.; Makino, K.; Millar, J.B.
The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle
Genes Dev.
11
1008-1022
1997
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Shiozaki, K.; Shiozaki, M.; Russell, P.
Mcs4 mitotic catastrophe suppressor regulates the fission yeast cell cycle through the Wik1-Wis1-Spc1 kinase cascade
Mol. Biol. Cell
8
409-419
1997
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Samejima, I.; Mackie, S.; Warbrick, E.; Weisman, R.; Fantes, P.A.
The fission yeast mitotic regulator win1+ encodes an MAP kinase kinase kinase that phosphorylates and activates Wis1 MAP kinase kinase in response to high osmolarity
Mol. Biol. Cell
9
2325-2335
1998
Schizosaccharomyces pombe (O74304), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Styrkarsdottir, U.; Egel, R.; Nielsen, O.
Functional conservation between Schizosaccharomyces pombe ste8 and Saccharomyces cerevisiae STE11 protein kinases in yeast signal transduction
Mol. Gen. Genet.
235
122-130
1992
Schizosaccharomyces pombe (P28829), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Wang, Y.; Xu, H.P.; Riggs, M.; Rodgers, L.; Wigler, M.
Byr2, a Schizosaccharomyces pombe gene encoding a protein kinase capable of partial suppression of the ras1 mutant phenotype
Mol. Cell. Biol.
11
3554-3563
1991
Schizosaccharomyces pombe (P28829)
Manually annotated by BRENDA team
Sengar, A.S.; Markley, N.A.; Marini, N.J.; Young, D.
Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharomyces pombe
Mol. Cell. Biol.
17
3508-3519
1997
Schizosaccharomyces pombe (Q10407), Schizosaccharomyces pombe
Manually annotated by BRENDA team
Zhou, X.; Ma, Y.; Sugiura, R.; Kobayashi, D.; Suzuki, M.; Deng, L.; Kuno, T.
MAP kinase kinase kinase (MAPKKK)-dependent and -independent activation of Sty1 stress MAPK in fission yeast
J. Biol. Chem.
285
32818-32823
2010
Schizosaccharomyces pombe (O14299), Schizosaccharomyces pombe (O74304), Schizosaccharomyces pombe, Schizosaccharomyces pombe 972 (O14299), Schizosaccharomyces pombe 972 (O74304)
Manually annotated by BRENDA team